Department of Neurosciences, University of New Mexico-Health Sciences Center, School of Medicine, NM, USA.
Neuromodulation. 2012 Nov-Dec;15(6):520-6; discussion 526. doi: 10.1111/j.1525-1403.2012.00462.x. Epub 2012 Jun 1.
Current research indicates that chronic peripheral neuropathic pain includes a role for glia and the actions of proinflammatory factors. This review briefly discusses the glial and cytokine responses that occur following peripheral nerve damage in support of utilizing anti-inflammatory cytokine interleukin-10 (IL-10) therapy to suppress chronic peripheral neuropathic pain. SPINAL NONVIRAL INTERLEUKIN-10 GENE THERAPY: IL-10 is one of the most powerful endogenous counter-regulators of proinflammatory cytokine function that acts in the nervous system. Subarachnoid (intrathecal) spinal injection of the gene encoding IL-10 delivered by nonviral vectors has several advantages over virally mediated gene transfer methods and leads to profound pain relief in several animal models. NONVIRAL GENE DELIVERY: Lastly, data are reviewed that nonviral deoxyribonucleic acid (DNA) encapsulated by a biologically safe copolymer, poly(lactic-co-glycolic) acid (PLGA), thought to protect DNA, leads to significantly improved therapeutic gene transfer in animal models, which additionally and significantly extends pain relief.
The impact of these early studies exploring anti-inflammatory genes emphasizes the exceptional therapeutic potential of new biocompatible intrathecal nonviral gene delivery approaches such as PLGA microparticles. Ultimately, ongoing expression of therapeutic genes is a viable option to treat chronic neuropathic pain in the clinic.
目前的研究表明，慢性周围神经性疼痛包括神经胶质细胞和促炎因子的作用。这篇综述简要讨论了周围神经损伤后发生的神经胶质细胞和细胞因子反应，以支持利用抗炎细胞因子白细胞介素-10（IL-10）治疗来抑制慢性周围神经性疼痛。脊髓非病毒白细胞介素-10 基因治疗：IL-10 是作用于神经系统的最强大的内源性促炎细胞因子功能的反向调节剂之一。通过非病毒载体进行蛛网膜下腔（鞘内）脊髓注射编码 IL-10 的基因具有优于病毒介导的基因转移方法的几个优点，并导致几种动物模型中的疼痛明显缓解。非病毒基因传递：最后，回顾了数据，非病毒脱氧核糖核酸（DNA）被生物安全共聚物聚（乳酸-共-乙醇酸）（PLGA）包裹，据认为可以保护 DNA，从而导致在动物模型中显著改善治疗性基因转移，此外还显著延长了疼痛缓解时间。结论：这些早期探索抗炎基因的研究的影响强调了新的生物相容的鞘内非病毒基因传递方法（如 PLGA 微粒）的卓越治疗潜力。最终，治疗性基因的持续表达是治疗临床慢性神经性疼痛的可行选择。
